2000 Fiscal Year Final Research Report Summary
Prevention and elucidation of the ototoxicity of interferon used for the treatment of hepatitis C
| Project/Area Number |
11671687
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Otorhinolaryngology
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| Research Institution | Nagasaki University |
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Principal Investigator |
TANAKA Fujinobu Nagasaki University, School of Medicine, Assistant, 医学部, 助手 (00284688)
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| Co-Investigator(Kenkyū-buntansha) |
KOBAYASHI Toshimitsu Nagasaki University, School of Medicine, Professor, 医学部, 教授 (80133958)
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| Project Period (FY) |
1999 – 2000
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| Keywords | interferon / mouse / ABR / EP / subcutaneous injection / intravenous injection / intraperitoneal injection |
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| Research Abstract |
Interferon (IFN) is widely used for the treatment of hepatitis type C.Its ototoxicity has been considered to be one of the side effect by some investigators (Kanda, et al 1994). The aim of this investigation is to evaluate the mechanism of ototoxicity of IFN and to establish the prophylaxis by means of animal experiments. The IFN (Recombinant Mu IFN-β) was administrated by intravenous injection, intraperitoneal injection and subcutaneous injection. As the cochlea of mice does not protrude into the middle ear cavity, administration into the perilymphatic space is not possible.
IFN at a dose of 500000IU/kg was administrated intravenously to mice having body weight of 20g in average. The dose was about 50-100 times as for human for one day. The threshold of ABR in response to the stimulus sound of click, 4 kHz tone burst and 8 kHz tone burst were measured before administration, 30 minutes, 120 minutes, 180 minutes and 1 weeks after administration. The thresholds did not show any remarkable change. In the case with intraperitoneal and subcutaneous administration, 1000000 IU/kg was injected to 20g weighted mice for 21 days. The ABR thresholds were compared to that of control group in which control solution were administrated by the same technique. There were no remarkable difference in the threshold of ABR to click, 4 kHz tone burst and 8 kHz tone burst between the IFN group and the control group. The endocochlear DC potential (EP) was measured in the subcutaneous injection group, but there were no significant difference between IFN group and control group. These preliminary data showed no remarkable histological change. The results obtained in the present investigation failed to show that IFN is toxic to the cochlea.
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